Abstract
BackgroundThe emergence of influenza viruses resistant to anti-influenza drugs is a threat to global public health. The Korea Centers for Disease Control and Prevention operates the Korea Influenza and Respiratory Viruses Surveillance System (KINRESS) to monitor epidemics of influenza and Severe Acute Respiratory Infection (SARI) to identify mutated influenza viruses affecting drug resistance, pathogenesis, and transmission.MethodsOropharyngeal swab samples were collected from KINRESS and SARI during the 2018–2019 season. The specimens confirmed influenza virus using real-time RT-PCR on inoculated MDCK cells. HA and NA sequences of the influenza viruses were analyzed for phylogeny and mutations. Neuraminidase inhibition and hemagglutination inhibition assays were utilized to characterize the isolates.ResultsTwo A(H1N1)pdm09 isolates harboring an H275Y substitution in the neuraminidase sequence were detected in patients with acute hematologic cancer. They had prolonged respiratory symptoms, with the virus present in the respiratory tract despite oseltamivir and peramivir treatment. Through the neuraminidase inhibition assay, both viruses were found to be resistant to oseltamivir and peramivir, but not to zanamivir. Although hemagglutinin and neuraminidase phylogenetic analyses suggested that the 2 A(H1N1)pdm09 isolates were not identical, their antigenicity was similar to that of the 2018–19 influenza vaccine virus.ConclusionsOur data indicate the utility of monitoring influenza-infected immunocompromised patients in general hospitals for the early detection of emerging neuraminidase inhibitor-resistant viruses and maintaining continuous laboratory surveillance of patients with influenza-like illness in sentinel clinics to monitor the spread of such new variants. Finally, characterization of the virus can inform the risk assessment for future epidemics and pandemics caused by drug-resistant influenza viruses.
Highlights
The emergence of influenza viruses resistant to anti-influenza drugs is a threat to global public health
Neuraminidase inhibitors (NAIs)-resistant virus has been rarely observed since 2000, the Korea Centers for Diseases Control and Prevention (KCDC), through the Korea Influenza and Respiratory Viruses Surveillance System (KINRESS), identified oseltamivir and peramivir-resistant A(H1N1)pdm09 viruses harboring the H275Y NA variation in patients with acute lymphoblastic leukemia and relapsed lymphoma hospitalized in the same general hospital, with both exhibiting prolonged virus excretion
Van der Vries et al [20] demonstrated that A(H1N1)pdm09 virus-infected immunocompromised ferrets exhibited prolonged virus replication despite antiviral therapy, along with the H275Y substitution observed in the virus population from day 8 onwards only in ferrets that received oseltamivir
Summary
The emergence of influenza viruses resistant to anti-influenza drugs is a threat to global public health. The Korea Centers for Disease Control and Prevention operates the Korea Influenza and Respiratory Viruses Surveillance System (KINRESS) to monitor epidemics of influenza and Severe Acute Respiratory Infection (SARI) to identify mutated influenza viruses affecting drug resistance, pathogenesis, and transmission. The Korea Centers for Diseases Control and Prevention (KCDC) has operated the Korea Influenza and Respiratory Viruses Surveillance System (KINRESS) to monitor epidemic features of influenza viruses and analyze virus characteristics, including drug resistance, since 2000. NAI-resistant viruses were identified in cases in which influenza virus was continuously detected following NAI treatment of hospitalized, immunosuppressed patients, rather than in clinical outpatients [9]. Drug-resistant A(H1N1)pdm viruses were detected via the KINRESS in patients with acute hematologic cancer not exhibiting recovery despite oseltamivir and peramivir administration; these were characterized genetically and antigenically following isolation
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